Israel Medical Association Journal

Background: Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder characterized by inattention, impulsivity and hyperactivity. Recently, increases in ADHD prevalence and methylphenidate use have been reported. There is evidence that children and adolescents use ADHD medication only during the school year. 

Objectives: To investigate trends in methylphenidate dispensing over a period of 3 years (2010–2012) at the monthly level and to investigate whether there is any monthly variation, especially during the summer season.

Methods: The database of Clalit Health Services (the largest of the four health funds in Israel) was used to identify (i) patients aged 6–17 years with a diagnosis of ADHD, and (ii) methylpenidate dispensation during the period 2010–2012. 

Results: Among children aged 6–17 years diagnosed with ADHD, 43% were treated with methylphenidate. For the period 2010 to 2012 there was an annual drop in methylphenidate dispensing, beginning in June and continuing through the 2 months of summer vacation, with a 2.5-fold reduction from July as compared to May. This decline was consistently followed by a rise in medications dispensed starting August. A similar small drop was observed during the Passover school vacation. The summer drop decreased over the years.

Conclusions: Our findings showed a decrease in the number of methylphenidate prescriptions dispensed during the summer months and Passover as compared to the rest of the year. However, this phenomenon appears to be decreasing. Given that ADHD is a chronic disease state that can effectively be managed with pharmacotherapy, discontinuation of treatment may be harmful for patients and should be considered only on a patient-by-patient basis.

 

Background: Strong evidence suggests that in order to prevent irreversible testicular damage surgical correction (orchidopexy) for undescended testis (UDT) should be performed before the age of 1 year. 

Objectives: To evaluate whether orchidopexy is delayed in our medical system, and if so, to explore the pattern of referral for orchidopexy as a possible contributing factor in such delays. 

Methods: We conducted a retrospective chart review of all children who underwent orchidopexy for UDT between 2003 and 2013 in our institution. We collected data on the age at surgery and the child's health insurance plan. We also surveyed pediatricians from around the country regarding their pattern of UDT patient referral to a pediatric urologist or surgeon for surgical correction.

Results: A total of 813 children underwent orchidopexy in our institute during the study period. The median age at surgery was 1.49 years (range 0.5–13). Only 11% of the children underwent surgery under the age of 1 year, and 53% between the ages of 1 and 2 years. These findings were consistent throughout the years, with no difference between the four health insurance plans. Sixty-three pediatricians who participated in the survey reported that they referred children to surgery at a median age of 1 year (range 0.5–3 years).

Conclusions: Our results demonstrate delayed orchidopexy in our medical system. There is a need to improve awareness for early specialist consultation in order to facilitate earlier surgery and better care.

 

Background: Antibiotic treatment of Clostridium difficile infection (CDI) has a high failure rate. Fecal microbiota transplantation (FMT) has proven very effective in treating these recurrences. 

Objectives: To determine which method of fecal microbiota transplantation (upper or lower gastrointestinal) and which type of donor (a relative or unrelated) is superior.

Methods: This is a retrospective analysis of treatment protocols and outcomes in 22 patients with refractory or recurrent CDI who underwent FMT at two Israeli facilities. Each center used a different donor type, stool preparation and method of delivery. The Tel Aviv Sourasky Medical Center used unrelated fecal donors and frozen stool samples and delivered them primarily (92%) via the lower gastrointestinal (GI) tract. Shaare Zedek Medical Center used fresh donor stool of relatives and delivered them primarily (90%) via the upper GI tract.

Results: FMT had an overall 2 month cure rate of 89%. Patients treated with FMT that was executed through the lower GI tract recovered faster from the infection (1.6 ± 1.08 vs. 2.4 ± 1 days for the upper tract, P = 0.03). The results also showed that patients who received lower GI tract FMTs were more likely to be cured of CDI (100% vs. 75% for upper tract FMTs, P = 0.16). Five patients (22%) died of CDI/FMT-unrelated causes and two (10%) died of CDI/FMT-related causes during the study period.

Conclusions: Lower GI tract FMT is a safe and effective treatment for refractory and recurrent CDI, and yields quicker results than upper GI tract FMT. 

 

Background: Despite the large volume of evidence on the management of retained products of conception (RPOC), there are virtually no data regarding the optimal time frame of surgical intervention in case of RPOC.

Objectives: To examine whether the time interval between spontaneous vaginal delivery or pregnancy termination and the uterine evacuation due to pathologically confirmed RPOC influences the reproductive outcome.

Methods: We retrospectively reviewed all the records of women who were admitted to our department due to pathologically confirmed RPOC following either spontaneous vaginal delivery or pregnancy termination between January 2000 and December 2010. Based on the median time from delivery or pregnancy termination until the operative intervention in the study group, patients were stratified into two groups: early intervention (< 3 weeks) and late intervention (> 3 weeks). Reproductive outcomes were compared between the two study groups. 

Results: Reproductive outcomes were analyzed in 172 patients with pathologically confirmed RPOC. Of them, 95 (55.2%) were included in the early intervention group and 77 (44.8%) in the late intervention group. There were no significant differences in the conception rate, mean time to conception, and the occurrence rate of a new infertility problem in women with early surgical intervention compared to those with late surgical intervention (P > 0.05). Furthermore, there was no significant difference between the groups in the pregnancy outcomes following RPOC. 

Conclusions: Early surgical intervention in women with pathologically confirmed RPOC following spontaneous vaginal delivery or pregnancy termination yields the same reproductive outcomes as late surgical intervention.

 

Background: Automated breast volumetric sonography (ABVS) is a new technology with various possible applications.

Objectives: To compare ABVS and breast magnetic resonance imaging (MRI) in the surveillance of women with BRCA1/2 gene mutation carriers.

Methods: We conducted a prospective study in Jewish female BRCA1/2 mutation carriers who underwent breast MRI and ABVS. The results of both exams performed 6 months apart or less, and relevant clinical data, were reviewed. The BIRADS results were divided into three subgroups according to subsequent expected management: BIRADS 1-2 (normal study), BIRADS 3 (probably benign finding), and BIRADS 4 and 5 (suspicious findings). BIRADS 0 and 6 scores were excluded from the study. Distribution of ABVS and MRI BIRADS scores were compared using McNemar's test, and concordance was calculated using the Cohen kappa test.

Results: Overall, 68 women, 40 BRCA1 and 28 BRCA2 mutation carriers, age range 26–69 (mean 44.55 ± 12.1 years), underwent 79 paired ABVS and MRI examinations. McNemar's test calculations showed no significant difference between MRI and ABVS BIRADS score distribution. Cohen’s kappa test resulted in k = 0.158, an agreement that can be described as only "slight agreement" between both modalities. Of 14 discordant cases there was one cancer, revealed by MRI and not by ABVS performed 6 months prior to MRI.

Conclusions: ABVS showed slight agreement with MRI in BRCA1/2 mutation carriers. These preliminary results on a small group of healthy high risk patients suggest that the diagnostic abilities of ABVS are inferior to MRI. Further studies encompassing larger groups are needed.

 

Background: Although 5-amino-salycilic acids (5-ASA) are often used with corticosteroid treatment in moderate-to-severe ulcerative colitis, the value of continuing/initiating 5-ASA in this clinical setting has not been explored. 

Objectives: To investigate the impact of a combination 5-ASA+corticosteroid therapy on the outcome of hospitalized patients with acute moderate-severe ulcerative colitis. 

Methods: We conducted a retrospective study of patients hospitalized with moderate-severe ulcerative colitis in two centers, Israel and South Korea. Patients were classified into those who received 5-ASA and corticosteroids and those who received corticosteroids alone. Analysis was performed for each hospitalization event. The primary outcome was the rate of treatment failure defined as the need for salvage therapy (cyclosporin-A/infliximab/colectomy). The secondary outcomes were 30 days re-admission rates, in-hospital mortality rates, time to improvement, and length of hospitalization. 

Results: We analyzed 209 hospitalization events: 151 patients (72%) received 5-ASA+corticosteroids and 58 (28%) corticosteroids alone. On univariate analysis the combination therapy group had a lower risk for treatment failure (11% vs. 31%, odds ratio 0.28, 95% confidence interval 0.13–0.59, P = 0.001). However, this difference disappeared on multivariate analysis, which showed pre-admission oral corticosteroid treatment to be the most significant factor associated with the need for salvage therapy. 

Conclusions: A signal for possible benefit of a combination 5-ASA and corticosteroids therapy was found, but was confounded by the impact of pre-admission corticosteroid treatment. 

 

Systemic sclerosis (SSc) is characterized by extensive collagen deposition, microvasculopathy and autoantibodies. All three features can be promoted by activation of T cells and B cells. T cells are of Th2 type producing profibrotic cytokines IL-4 and IL-13 and inducing dendritic cell maturation that promotes Th2 response. B cells are overactivated and promote fibrosis by autoantibodies that activate fibroblasts or inhibit the degradation of extracellular matrix. They also promote fibrosis by cell-cell contact with fibroblasts or dendritic cells. B cells, through autoantibodies, may promote vasoconstriction and obliterative vasculopathy. They may also sustain activation of T cells by functioning as antigen-presenting cells. An immunoregulatory subset of B cells, namely IL-10-producing Bregs, is decreased in SSc. Finally, B cells have a critical role in animal models of SSc. All this evidence suggests an important role for B cells in the pathogenesis of SSc and makes B cells a potential target for therapeutic intervention in this disease. 

 

Autoimmune diseases constitute a diverse group of disorders characterized by cellular and humoral responses against self. The humoral autoimmune responses are directed against various cellular and extracellular components. These responses are highly specific for each autoimmune disease and result in the production of autoantibodies that characterize certain disease entities, representing a valuable tool for the diagnosis of autoimmune diseases. Furthermore, certain autoantibodies are helpful in the prognosis of disease development, progression and severity, as well as in the classification of patients with distinct disease subtypes. Today, the value of autoantibodies in the follow-up of patients is limited, but preliminary data suggest that they may be useful in predicting response to treatment. 

Women who carry the BRCA gene mutation have an up to 80% chance of developing cancer, primarily of breast and ovarian origin. Confirmation of carrier status is described by many women as an overwhelming, life-changing event. Healthy individuals harboring a BRCA mutation constitute a high risk population with unique needs, often overlooked by health authorities. As such, we felt the need to create a specialized service dedicated specifically to this high risk population. The clinic staff comprises an experienced multidisciplinary team of health professionals who can support the medical and emotional needs of this population. Since its inception in 2001 the clinic has served 318 women. The mean age of patients is 46 years. With a median follow-up of 46 months, 21 women have developed malignancies, including 17 breast cancers, 1 ovarian cancer and 3 additional cancers. All but one of the patients above the age of 40 underwent bilateral salpingo-oophorectomy (BSO). The median and mean ages at BSO were 46.5 and 48 years, respectively (range 33–68). However, only 28.3% underwent bilateral preventive mastectomy. A multidisciplinary clinic for BRCA mutation carriers provides a “home” for this unique population with unmet needs. The high rate of BSO in women before natural menopause indicates that both the medical community and this population are aware of international guidelines supporting this procedure. We believe that a dedicated clinic, with a multidisciplinary team, is likely to contribute to the health, quality of life and survival of BRCA carriers.